Definition of a Neurotransmitter
A neurotransmitter is defined as a chemical messenger which is released from the synaptic terminal of a neuron at a chemical synapse that diffuses across the synaptic cleft and binds to and stimulates the post-synaptic membrane. In simple words, a neurotransmitter is a chemical messenger released from one nerve cell which makes its way to another nerve cell where it influences a particular chemical reaction to occur. Neurotransmitters control major body functions including movement, emotional response, and the physical ability to experience pleasure and pain.

     The neurotransmitters that are most familiar to the public are serotonin, norepinephrine, dopamine, acetylcholine, and GABA. Click on each link to find out how you can increase specific neurotransmitter levels through the use of natural supplements. If you would like to purchase some supplements, consider Hydroxytryptophan supplement to increase serotonin levels, and mucuna pruriens herb to increase dopamine levels. I have not found GABA supplements to be very effective in reducing anxiety although some people reports it helps them.

Types of Neurotransmitters
Neurotransmitters can be broadly classified into several categories:
Small molecule transmitters and neuroactive peptides. Around 10 small-molecule neurotransmitters are generally recognized: acetylcholine, 5 amines, and 3 or 4 amino acids,
Purines, (Adenosine, ATP, GTP and their derivatives).
Fatty acids
Neuroactive peptides have been found, among them neuropeptide Y and hormones such as leutenizing hormone.
Single ions, such as the mineral zinc are considered neurotransmitters by some.
Gases such as nitric oxide

Serotonin Neurotransmitter
Serotonin happens to be the most widely studied neurotransmitter since it helps regulate a vast range of psychological and biological functions. Serotonin (5-hydroxytryptamine or 5-HT) was first identified in 1948. The wide array extent of psychological functions regulated by serotonin involves mood, anxiety, libido, aggression, and thinking abilities. Other brain neurotransmitters, such as dopamine and norepinephrine, also influence mood and arousal. However, serotonin generally has different effects. For instance, excess amounts of serotonin cause relaxation, sedation, and a decrease in sexual drive. Prozac, a common antidepressant of the SSRI type, elevates serotonin levels in the brain. One of the common side effects of SSRIs is diminished sexual urge and sensation. There is a nutrient called 5-hydroxytryptophan 5-HTP that is the immediate precursor to serotonin. When ingested as a supplement, 5-HTP converts in the brain into serotonin. The substance 5-HTP is often used to treat depression and anxiety. I have noticed that 5-HTP supplements decrease sex drive and interest.

Dopamine neurotransmitter
Dopamine is one of the most important neurotransmitters involved in the human sexual response. Dopamine has a significant effect on sexual desire. Plus, elevation of dopamine levels often leads to an improvement in mood and alertness. A number of psychiatric disorders, particularly Parkinson's disease and mood disorders, are attributed to imbalances in dopamine levels. Dopamine is made from the amino acid tyrosine. Once produced, dopamine can, in turn, convert into the brain chemicals norepinephrine and epinephrine. Some of the natural supplements that increase dopamine levels include NADH and CDP-choline.

Acetylcholine neurotransmitter
Acetylcholine was the very first neurotransmitter to be identified back in the early 1900s. It is made simply from choline, a natural substance found in lecithin, and a two-carbon molecule called acetyl. Acetylcholine plays numerous roles in the nervous system. In the brain, acetylcholine is involved in learning and memory whereas in the genital organs, acetylcholine is released by the parasympathetic nerves. Acetylcholine helps in the release of nitric oxide, which leads to the relaxation of smooth muscles and engorgement of the genital organs. Nutrients that elevate levels of acetylcholine include choline and CDP-choline.

Norepinephrine neurotransmitter and Epinephrine
In the flaccid state of the penis, frequent release of norepinephrine from sympathetic nerves contracts the arteries in the penis and also contracts the smooth muscles of the corpora cavernosum. Therefore, in the normal state, norepinephrine keeps the penis soft. A relative predominance of norepinephrine-induced contraction over nitric oxide-mediated relaxation may contribute to erectile dysfunction. Two amino acids phenylalanine and tyrosine, sold as supplements, are converted into dopamine. Dopamine, in turn, is converted into norepinephrine, and then epinephrine. The ingestion of these amino acids elevates dopamine and norepinephrine levels, and hence will lead to alertness and mood elevation and increased sexual interest. However, excess amounts of norepinephrine and epinephrine may make it difficult to have erections. In addition, high amounts raise blood pressure, increase heart rate, and cause anxiety, irritability, and insomnia. Yohimbe, the natural sex booster from Africa, facilitates erections by blocking the inhibitory action of norepinephrine on the penis.

Nitric Oxide: Say Yes to NO
Nitric oxide (NO) is the most important neurotransmitter involved in the engorgement of genital organs leading to erections. I will mention NO several times Throughout this book, since some you will find herbs and nutrients that help in the formation of this chemical. For instance, the amino acid arginine can be metabolized into NO by an enzyme known as nitric oxide synthase. This conversion is done in endothelial cells, which are cells that line the inside of blood vessels. Ginseng, the popular herbal aphrodisiac, is also thought to increase NO levels. NO functions by activating an enzyme called guanylate cyclase. Guanylate cyclase, in turn, helps form cyclic guanosine monophosphate (cGMP). cGMP becomes the secondary messenger that causes smooth muscle relaxation, resulting in venous engorgement and erections. Under normal conditions, cGMP helps the smooth muscles surrounding the arteries of the penis and the smooth muscles of the corpus cavernosum to relax. This allows blood to easily flow into the penis. Any condition that interferes with the signaling of these messenger enzymes can quickly lead to the breakdown of the entire process and cause erectile dysfunction. Viagra works by blocking an enzyme that breaks down cGMP, hence more of this chemical is left to help dilate the genital arteries. Interestingly, having adequate levels of androgen hormones in the body makes it easier for the genital organs to respond to nitric oxide.
     Nitric oxide is a biological messenger molecule produced by one of the essential amino acids L-arginine by the catalytic action of the enzyme NO synthase (NOS). The dual role of nitric oxide as a protective or toxic molecule is due to several factors, such as; the isoform of NOS involved, concentration of NO and the type of cells in which it is synthesised, the availability of the substrate L-arginine, generation of guanosine 3,5'-cyclic monophosphate (cGMP) from soluble guanylate cyclase and the overall extra and intracellular environment in which nitric oxide is produced.

GABA neurotransmitter
In the adult central nervous system (CNS), gamma-amino butyric acid (GABA) is a predominant inhibitory neurotransmitter, and is involved in relaxation. Thus, dysfunction of the GABA system is implicated in the pathophysiology of several neuropsychiatric disorders, including anxiety and depression.
     In mammals, 16 different polypeptides (alpha1-alpha6, beta1-beta3, gamma1-gamma3, delta, epsilon, pi, and theta) have been identified, using recombinant DNA techniques, each of which is encoded by a distinct gene. The products of these genes assemble in diverse combinations to form a variety of receptor subtypes that have different sensitivities to a number of clinically relevant compounds, such as the benzodiazepines (BZs). 2. Based on a number of chromosomal mapping techniques, the majority of the GABA(A) receptor genes have been localized, in man, in four clusters on chromosomes 4, 5, 15, and the X. Furthermore, the genes that are present within these clusters have a conserved transcriptional orientation. It has, therefore, been proposed that the clusters arose largely as a consequence of two whole-genome doublings that occurred during chordate evolution, and that the ancestral cluster contained an "alpha-like," a "beta-like," and a "gamma-like" subunit gene.
     Piracetam is a derivative of GABA. Supplements of GABA are also available, however it is unclear how effectively a GABA supplement can cross the blood brain barrier.

Glutamate neurotransmitter
The role of glutamate receptors in synaptic transmission and excitotoxicity in the nervous system is well established. Recent evidence has emerged that glutamatergic mechanisms also exist in a wide variety of non-neuronal cells. In the case of thymocytes and lymphocytes, several types of glutamate receptor are expressed which can induce functional changes. Glutamate may serve as a signaling agent between the immune and nervous systems.

Histamine neurotransmitter
Histamine has many actions in both the periphery and in the central nervous system. In the lungs, histamine acts the smooth muscle of the smaller bronchioles to cause constriction, and reduced air flow. In the stomach, histamine is involved in acid secretion.

Neurotransmitter testing
A neurotransmitter test is available to measure the levels of major neurotransmitters including serotonin, norepinephrine, epinephrine, GABA and dopamine. This testing can be done by urine, blood, or a spinal tap to measure neurotransmitter levels in the spinal fluid. However, only in rare cases is it necessary to do neurotransmitter testing. Even if we know the blood level of these neurotransmitters, and we find a neurotransmitter deficiency, it offers little help in guiding therapy since neurotransmitter levels and neurotransmitter production fluctuates easily from day to day and hour to hour. Neurotransmitter testing is not a reliable way to determine how a person will respond to a particular medicines or supplement for conditions such as depressions, anxiety, ADHD, etc. Neurotransmitter testing could reveal a neurotransmitter imbalance that would be accurate for that particular time period only. Neurotransmitter testing is appropriate in cases of neurotransmitter imbalance or excess such as pheochrmocytoma and other clear cut medical conditions.

Q. I have read many of your articles and am a frequent visitor to your web site. I respect your opinion and advice but I saw this quote 'As of February 2009, I am not convinced that testing for neurotransmitter levels adds to the clinical treatment of a patient'. and would like to share my experience. My daughter was unable to focus on her studies and suffered extreme fatigue. We had her tested for several things and nothing seemed to help. I found information that suggested her neurotransmitters may have been contributing to her condition. Several doctors refused to submit her to a urine and/or saliva test and finally we found a naturopath willing to submit the test and treat her depending on the results. She was severely unbalanced and a regimen was developed using vitamins and supplements to address the issue. In three months we noticed several changes for the better in her. She lost weight, had a better self-image, but most of all her ability to concentrate on any matter was improved. She has subsequently gone back to school and her grades have improved. We have high hopes that she will be able to complete her university education. BTW she is majoring in neuroscience. Hopefully someday there will be enough scientific evidence to encourage you to change your opinion. Thank you and keep up the good work.
   A. Many doctors, naturopaths and Oriental medicine doctors prescribe vitamins and supplements to their patients who end up improving. In almost all cases these improvements are done without neurotransmitter level testing. Neurotransmitter testing just adds to the cost of medical care, which most people in these tough economic times cannot afford. There may be cases where such testing is appropriate and helpful and we are glad your daughter was helped and we wish you and her well.
 

Monoamine neurotransmitter
These include serotonin, norepinephrine, GABA, glutamate, and dopamine. The monoamine hypothesis holds that mood disorders are caused by a depletion in one or more of these neurotransmitters.

Neurotransmitter metabolism
The process by which our bodies make, use, and break down neurotransmitters is extremely complicated. When there is a disruption within this process, abnormalities can occur in any of their essential functions.

Acetylcholine is derived from Choline
Serotonin [5-Hydroxytryptamine (5-HT)] is derived from  Tryptophan
GABA is derived from Glutamate
Histamine is derived from Histidine
Epinephrine, norepinephrine and dopamine are derived from Tyrosine
Adenosine is derived from ATP
Nitric oxide is derived from Arginine

Neurotransmitter release
Neurotransmitters are responsible for transmitting information across the synaptic gap between neurons. Neurotransmitters are stored in synaptic vesicles. When action potentials are conducted down an axon, synaptic vesicles attach themselves to the presynaptic membrane, then break open and spill neurotransmitter into the synaptic cleft. Neurotransmitters in the synaptic cleft attach to postsynaptic receptor sites and trigger an action potential in the postsynaptic membrane.  Some neurotransmitters attach to presynaptic neurotransmitter receptors (autoreceptors) located on the membrane (pre-synaptic membrane) of the cell that originally released them.

Neurotransmitter and taste alteration
Taste sensitivity is altered by changing levels of  neurotransmitters that are thought to be involved in depression. In a press release from the University of Bristol, Dr. Lucy F. Donaldson said, "we hope that using a taste test in depressed people will tell us which neurotransmitter is affected in their illness," and thus assist in treatment decisions. Neurotransmitters are chemicals that generate nerve signals in the brain. Serotonin, dopamine and noradrenaline are three that are believed to affect mood states. Some reports have linked changes in taste sensitivities with severe depression and anxiety. Donaldson and her associates explored taste changes among 20 healthy adults, before and after they were given the antidepressant Paxil, which raises the amount of serotonin available, and Edronax, which does the same for noradrenaline. The subjects' taste responses were determined by applying varying concentrations of "tastants" to the tip of the tongue using a cotton swab. After 5 seconds, subjects reported if they could taste the stimulus at that concentration. Paxil increased sensitivity to sweet and bitter tastes. Conversely, Edronax lowered taste thresholds to bitter and sour tastes. In the most anxious participants, taste sensations appeared to be blunted, with significantly higher recognition thresholds for bitter and salt taste."These results support an important and basic role for the neurotransmitters serotonin and noradrenaline in taste function and may explain why anxious and depressed individuals exhibit diminished appetite," the researchers add. Journal of Neuroscience, December 6, 2006.

Questions about natural supplements and how they influence neurotransmitter levels
Q.  I have been using Dr. Sahelian's formulated 5-HTP for some time now and it's been very good. My neurotransmitters became unbalanced just about when my hormones did in '02. A nightmare. That's when I changed over to a naturopath (a woman, too) and she has enlightened my to things I'd never known. Now things have so improved. I am very happy to know Dr. Sahelian (through his books). He is a very learned man.

Q. I currently go to a MD. He says there are no tests to measure neurotransmitters, so when he prescribes me anti-depressants it's a hit and miss basis. Effexor didn't work. I currently am trying Wellbutrin. Do you know of any tests to see which neurotransmitter is off and causing the depression I have?
   A. There are no routine blood tests to check neurotransmitter levels in the blood. There are advanced labs that can do this but there is no guarantee that blood levels reflect the levels in the central nervous system or would be useful in a practical manner in guiding the choice of an antidepressant. It may take trail and error to find the ideal way to treat depression with natural methods or antidepressant drugs.

Q. I’d appreciate a list of herbs that modulate or reduce catecholamine neurotransmitters (both epinephrine and norepinephrine) as well as any known to support PNS activity.
   A. See the links for dopamine at the top of the page.

Q. My 32 y.o. daughter has been on Abilify for several years and wants to get off as she is concerned about side effects. She had neurotransmitter tests which showed she was low in dopamine and serotonin. Do you have supplements for this?
   A. There are countless hormones, substances and chemicals in the body that have an influence on mood, behavior, and cognitive abilities. Sometimes focusing on one or two oversimplifies the complexity of all the physiological functions of the body. Nevertheless, you will find links to the respective neurotransmitters.

Q. I have had testing done by a company (I won't mention the name) for neurotransmitter levels. They point out that the neurotransmitters undergo a daily variation and are greatly influenced by uncontrolled daily stressors. They have people test a certain time after waking but before going to work, etc. They have done something like half million reference tests on healthy individuals to get their optimal ranges. Since they started with around 300 tests, those optimal ranges have changed very little, so they have stood the test of time. They also make it very clear that neurotransmitters are present in the central and peripheral nervous system, so the tests are not diagnostic, but are biomarkers. There are trends that show up consistently relating to certain symptoms or conditions. I think in general maybe you can't measure neurotransmitter levels, but there are many research papers that say otherwise. I think it's all about how you do it, as in the above mentioned testing. One article I will reference was recently in the Townsend Letter: "Urinary Neurotransmitter Analysis as a Biomarker for Psychiatric Disorders" by Amnon Kahane, MD.
   A. There is still a wide gap between testing for neurotransmitter levels and determining which form of therapy and in what dosage would work best. Neurotransmitter levels can be influenced on a daily basis by diet, activity level, sleep patterns, stress, and a number of factors. As of February 2009, I am not convinced that testing for neurotransmitter levels adds to the clinical treatment of a patient.

Q. My name is Marty L. Hinz, MD, President Clinical Research, NeuroResearch Clinics, Inc. Cape Coral, Florida USA. There is a recently published peer reviewed literature relating to neurotransmitters and neurotransmitter testing. I attached a chapter from a new medical text book edited by Ingrid Kohlstadt, MD of Johns Hopkins Medical School and a writing by the University of Minnesota Medical School that is in the May 2009 Journal of NeuroPsychiatry. Of concern is laboratory companies out there that are promoting neurotransmitter testing trying to test basic neurotransmitter science that is not supported by the literature and these peer reviewed articles.
   A. A review of the chapter written by D. Marty L. Hinz, M.D. that was attached in the email leads to a section that says,

TABLE 29.1
The “Generic Amino Acid Dosing Protocol” (milligrams of 5-HTP / milligrams tyrosine) If relief of symptoms is not obtained with level 3 dosing, obtain urinary neurotransmitter testing. Use of proper levels of cofactors and sulfur amino acids is required for optimal results
LEVEL  AM         NOON         4 PM           7 PM
1      150/1500                       150/1500
2      150/1500  150/1500    300/1500
3      150/1500 150/1500     300/1500    300/1500

The generic protocol developed for treatment of neurotransmitter dysfunction disease relating to the catecholamine system and/or serotonin system involves the use of tyrosine, 5-HTP, and cofactors. Results do not appear to be dependent on taking the amino acids with or without food. The following cofactors need to be used along with the amino acid precursors:
• Vitamin C 1000 mg/day
• Vitamin B6 75 mg/day
• Calcium 500 mg 500 mg/day

In addition
• Cysteine 4500 mg/day in equally divided doses
• Selenium 400 mcg/day
• Folic acid 2000 to 3000 mcg/day

   Dr. Sahelian comments: I am concerned that many people on this protocol will have heart rhythm disturbances and insomnia. Tyrosine can cause heart rhythm problems in as a low a dosage as 250 mg. I also do not believe that urinary neurotransmitter testing is necessary, it is just an additional expense. I have not seen any peer reviewed published research that demonstrates that repeatedly testing urinary neurotransmitter levels leads to a better outcome for patients who are depressed.
   Many people with mild to moderate depression may find mood elevation with using 50 to 100 mg of 5-HTP supplements bought online or in a health food store without incurring the expense of doctor visits and neurotransmitter testing. Others benefit from SAM-e and St. John's wort. Some people who promote these kinds of tests are likely to monetarily profit from the testing. There have been countless people who have recovered from their depression without incurring the costs of such urinary neurotransmitter testing.
   I am also concerned about the high dosages of selenium. Studies have shown that high amounts, usually over 100 mcg a day, can reduce longevity.